Brain Pathology Case of the Month - February 1997
FINAL DIAGNOSIS: ANAPLASTIC EPENDYMOMA
Ependymomas are the third most common brain tumor in the pediatric population. Over 90% of these cases are intracranial, while in adults, most ependymomas occur in the spinal cord. In children, most intracranial ependymomas are infratentorial, where their relationship to the floor of the fourth ventricle often makes complete resection difficult. Supratentorial ependymomas may occur in relation to the lateral ventricles or in the midline, as in this case. It has been noted that supratentorial midline ependymomas are more likely to exhibit clear-cell morphology (20) , which may so dominate the histologic picture as to warrant a diagnosis of clear-cell variant of ependymoma. In the case presented here, only focal areas showed clear-cell histology, while most areas showed the more "classic" architecture of a cellular ependymoma. This case also had numerous areas of necrosis, significant endothelial proliferation and an extrememly high mitotic rate: sometimes as many as 5 mitotic figures could be found in one high power field.
The histologic features required for the diagnosis of anaplastic ependymoma remain, to some degree, controversial (1). This is primarily because numerous retrospective clinical studies have yielded conflicting results regarding the prognostic significance of the diagnosis of "anaplastic ependymoma". In some studies, anaplasia had prognostic significance (3, 4, 8, 10, 18, 19) , while other studies have not shown significant differences in outcome for patients with ependymoma or anaplastic ependymoma (2, 5, 6, 9, 11, 12, 14, 15).
Most of these latter studies, however, did note a trend for worse outcome in anaplastic ependymomas.
Several studies have analyzed specific anaplastic features as possible prognostic indicators, but these too, have failed to clarify the issue (5, 6, 10-12, 16, 17) . In a recent study of 37 cases, necrosis was associated with a poor outcome by univariant analysis, but was not significant by multivariant analysis (5) . A larger study of 298 cases, found that high mitoses (>20 per ten high power field)
were prognostically significant only in supratentorial ependymomas (16, 17) . Nazar et. al., stratified infratentorial ependymomas into three groups based on mitoses, necrosis and dense cellularity and showed mitotic index to be the most important factor (10) , however, other studies using this method have not replicated these findings (6, 7) . To highlight the variable outcome in anaplastic ependymomas, Ross and Rubenstein (13) studied 15 cases of anaplastic ependymomas and found a 58% 5 year survival. They concluded that histologic criteria do not predict malignant behavior. What is apparent from these studies is that specific anaplastic features such as mitoses, necrosis and endothelial proliferation do not have the same well-defined relationship to prognosis as do the same features in fibrillary astrocytomas (5, 6, 10, 11, 16, 17) . Most studies have concluded that extent of resection is the critical prognostic factor (6, 7, 10, 11, 14, 19) . Following resection, most intracranial ependymomas are treated with local radiation; the use of whole brain or cranio-spinal radiation in the absence of documented CSF spread remains controvesial, especially in infants. Chemotherapy, at this time, has not been show to alter outcome.
- Burger P, Scheithauer B (1994) Tumors of the central nervous system. Atlas of tumor pathology 3rd series, Fascicle 10, Armed Forces Institute of Pathology: Washington D.C.
- Dohrmann GJ, Farwell JR, Flannery JT (1976) Ependymomas and ependymoblastomas in children. J Neurosurg 45: 273-283
- Ernestus RI, Schroder R, Stutzer H, Klug N (1996) Prognostic relevance of localization and grading In intracranial ependymomas of childhood. Childs Nerv Syst 12: 522-526
- Figarella-Branger D, Gambarelli D, Dollo C, Devictor B, Perez-Castillo AM, Genitori L, Lena G, Choux M, Pellissier JF (1991) Infratentorial ependymomas of childhood. Correlation between histological features, immunohistological phenotype, silver nucleolar organizer region staining values and post-operative survival in 16 cases. Acta Neuropathol 82: 208-216
- Gerszten PC, Pollack IF, Martinez AJ, Lo KH, Janosky J, Albright AL (1996) Intracranial ependymomas of childhood - lack of correlation Of histopathology and clinical outcome. Pathol Res Prac 192: 515-522
- Healey EA, Barnes PD, Kupsky WJ, Scott RM, Sallan SE, Black PM, Tarbell NJ (1991) The prognostic significance of postoperative residual tumor in ependymoma. Neurosurgery 28: 666-671; discussion 671-662
- Ikezaki K, Matsushima T, Inoue T, Yokoyama N, Kaneko Y, Fukui M (1993) Correlation of microanatomical localization with postoperative survival in posterior fossa ependymomas. Neurosurgery 32: 38-44
- Kovalic JJ, Flaris N, Grigsby PW, Pirkowski M, Simpson JR, Roth KA (1993) Intracranial ependymoma long term outcome, patterns of failure. J Neuro-Onc 15: 125-131
- Lyons MK, Kelly PJ (1991) Posterior fossa ependymomas: report of 30 cases and review of the literature. Neurosurgery 28: 659-664; discussion 664-655
- Nazar GB, Hoffman HJ, Becker LE, Jenkin D, Humphreys RP, Hendrick EB (1990) Infratentorial ependymomas in childhood: prognostic factors and treatment. J Neurosurg 72: 408-417
- Pollack IF, Gerszten PC, Martinez AJ, Lo KH, Shultz B, Albright AL, Janosky J, Deutsch M (1995) Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery 37: 655-666; discussion 666-657
- Rorke LB (1987) Relationship of morphology of ependymoma in children to prognosis. Prog Exp Tumor Res 30: 170-174
- Ross GW, Rubinstein LJ (1989) Lack of histopathological correlation of malignant ependymomas with postoperative survival. J Neurosurg 70: 31-36
- Rousseau P, Habrand JL, Sarrazin D, Kalifa C, Terrier-Lacombe MJ, Rekacewicz C, Rey A (1994) Treatment of intracranial ependymomas of children: review of a 15-year experience. Int J Radiat Oncol Biol Phys 28: 381-386
- Salazar OM, Rubin P, Bassano D, Marcial VA (1975) Improved survival of patients with intracranial ependymomas by irradiation: dose selection and field extension. Cancer 35: 1563-1573
- Schiffer D, Chio A, Cravioto H, Giordana MT, Migheli A, Soffietti R, Vigliani MC (1991) Ependymoma: internal correlations among pathological signs: the anaplastic variant. Neurosurgery 29: 206-210
- Schiffer D, Chio A, Giordana MT, Migheli A, Palma L, Pollo B, Soffietti R, Tribolo A (1991) Histologic prognostic factors in ependymoma. Childs Nerv Syst 7: 177-182
- Shaw EG, Evans RG, Scheithauer BW, Ilstrup DM, Earle JD (1987) Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients. Int J Radiat Oncol Biol Phys 13: 1457-1462
- Vanuytsel LJ, Bessell EM, Ashley SE, Bloom HJ, Brada M (1992) Intracranial ependymoma: long-term results of a policy of surgery and radiotherapy. Int J Radiat Oncol Biol Phys 23: 313-319
- Zulch K (1986) Brain tumors, their biology and pathology, 3rd, Springer Publishing Company: New York
Contributed by Ronald L. Hamilton, MD.